Obesity and diabetes currently account for approximately 300,000 early deaths per year in the U.S., comparable to smoking. Obesity and diabetes have reached epidemic proportions, with high mortality rates and associated economic costs. The current rate of increase of metabolic disease is sufficiently high to be classified by WHO (World Health Organization) as an epidemic, and as such represents the first non-infectious epidemic.
Diet therapy almost always fails as a measure for treating obesity as about 98% of those who achieve weight loss by diet, regain it within 5 years.
There is currently a dearth of approved effective pharmacotherapies. At least nine known therapies for obesity have been approved by the FDA. It is believed that seven of these have been withdrawn from the market due to toxicity or other failure. Sales of the remaining two therapies, orlistat and sibutramine, are low due to low efficacy and unpleasant side effects. The high demand for therapies is however reflected in annual expenditures of $32B in the U.S. alone for over-the-counter therapies, nutritional therapies, and associated “fringe” medicines.
Surgery is currently the most effective therapy for obesity and diabetes. Of approximately 20 different surgeries that have been attempted for the treatment of morbid obesity, 6 remain, the most successful being the Roux-en-Y gastric bypass (RYGBS), with biliopancreatic diversion. The bariatric procedures currently used include Vertical Banded Gastroplasty (VBG); Gastric bypass using the Roux-en-Y anastomosis; Gastric banding; and the Mini gastric bypass. Vertical banded gastroplasty restricts the size of the stomach using a stapling technique. There is no rearrangement of the intestinal anatomy.
Gastric bypass using the Roux-en-Y anastomosis restricts the size of the stomach by stapling shut 90% of the lower stomach. The proximal intestinal anatomy is re-arranged, thereby bypassing the duodenum. Gastric banding involves placing a gastric band around the outside of the stomach. The stomach is not entered.
Mini gastric bypass utilizes a laparoscopic approach in which the stomach is segmented, similar to a traditional gastric bypass. Instead of creating a Roux-en-Y anastomosis, the jejunum is anastomosed in continuity directly to the stomach, similar to a Billroth II procedure. The unique aspect of the procedure is not based on the laparoscopic approach, but rather the type of anastomosis used.
The biliopancreatic bypass procedure (“Scopinaro procedure”) consists of subtotal gastrectomy using a long Roux-en-Y procedure to divert the biliopancreatic juices into the distal ileum. The Biliopancreatic bypass with duodenal switch is essentially a variant of the biliopancreatic bypass. Instead of performing a distal gastrectomy, a “sleeve” gastrectomy is performed along the vertical axis of the stomach. The sleeve gastrectomy decreases the volume of the stomach and the parietal cell mass.
In 2003, approximately 140,000 such procedures were performed within the United States, up from 10,000 per year five years earlier. It is unlikely, due to the rate at which new surgeons can be trained and operating rooms made available, that this number could extend beyond approximately 200,000 per year in the near future. At the same time, the number of patients eligible for and in need of such surgery in the United States is at least 12 million, and depending upon criteria established largely by insurers, may be as high as 23 million.
Bariatric surgery is expensive, costing approximately $20,000, and complications requiring surgical correction are approximately 11%. Mortality rate is about 0.5-1.5%. Some patients eligible for bariatric surgery require presurgical weight loss to reduce operative risk and difficulty.
There is therefore an acute need for less expensive interventions, with durable effect, that can be performed faster and with less risk, but that mimic the benefits of bariatric surgery.
There is controversy however, over which aspects of the surgery are responsible for the observed efficacy. Elements of the surgery that are believed to contribute to this efficacy include gastric factors and intestinal factors. Gastric factors include reduced gastric size, increased sensations of gastric distension and reduced production of the orexigenic hormone, ghrelin. Intestinal factors include reduced absorptive area, shunting of unabsorbed calories to distal gut, shunting of bile to distal gut and persistence of digestible luminal signals in distal gut.
Several surgical techniques and devices directed to enhancing or replacing bariatric surgeries have concentrated upon inducing gastric factors that normally result responsive to surgery. Devices and procedures aimed at reducing actual gastric size include the Micropouch procedure as in U.S. Pat. No. 6,758,219, a constrictive coating applied to the outside of the stomach as in U.S. Pat. No. 6,572,627, and the vertical gastroplasty procedure as in U.S. Patent Publication No. 2004/0097989A1. Some devices attempt to bypass the accommodating volume and digestive environment of the stomach by the insertion of a gastric sleeve such as in U.S. Patent Publication No. 2004/0039452A1 and WIPO publication WO/2003086247A1.
Devices and procedures directed to restricting food influx into the stomach include banding devices such as and U.S. Patent Publication No. 2004/0049209A1, U.S. Patent Publication No. 2004/0097989A1, and U.S. Pat. No. 4,592,339 or other restrictors as in WO/2003086246A1. Other devices are directed to creating an artificial distension signal, either by occupying space, as with balloons such as in WO/200235980A3 and WO/2004019765A2 and other intragastric expanders as in U.S. Pat. Nos. 6,675,809 and 5,868,141.
Other approaches that aim to moderate rate of stomach emptying by local treatment of the pylorus, e.g. with pharmacologic agents, appear in U.S. Patent Publication No. 2004/0089313A1. U.S. Patent Publication No. 2004/0015201A1 is directed to moderating rate of stomach emptying with electro stimulation. Other approaches aim to mimic non-gastric aspects that may contribute to effects of RYGBS. These include the inhibition of digestion and absorption. These approaches apply an impermeable barrier between the chyme (undigested food) and the absorptive intestinal wall, for varying lengths of the intestine. In one known application, the barrier is applied as a liquid, or as a film bonded to the gut (see U.S. Pat. No. 4,315,509 and U.S. Patent Publication No. 2003/0191476A1). Sleeves of various configurations have been described in U.S. Pat. Nos. 4,501,264, 5,306,300 and 5,820,584, WO/2003094785A1, and WO/2004049982A2. The sleeves principally vary in their point of origination, some anchored within the stomach, and some distal. WO/03094785A1 provides a sleeve device anchored just below the esophageal sphincter to isolate the stomach as well as continuing as a barrier to absorption within the proximal small bowel.
Another device is based within the pylorus, with a tubular duodenal extension to delay intermixing of digestive enzymes with food exiting the stomach, as in U.S. Pat. No. 5,820,584. A flexible tubular screen has also been designed with a ring that is self-anchoring within the antrum, and a “brush-like” distal end that is subject to normal peristaltic forces to keep it extended within the gut. This device also aims to maintain separation between food and digestive juices and claims advantages over the devices of described in U.S. Pat. No. 4,315,509 to Smit and U.S. Pat. No. 4,501,264 Rockey. The sleeve of Rockey was described to generally isolate any viscera from its detrimental contents, but in the context of obesity, was described only as being placed within the stomach to limit digestive processes therein. Most recently, the bariatric sleeve of Levine et al., WO/2004049982A2 and U.S. Publication No. 2004/0107004 is described as anchored in the stomach. Anchors have also been designed that sit just distal to the pylorus within the duodenum. The intent of such devices is also to separate food from the absorptive duodenum.
The working principles of the above devices are essentially twofold: to restrict meal capacity and/or flow, and/or to apply a barrier to digestion and/or absorption.
Devices currently marketed include banding devices. These have lesser efficacy in the treatment of morbid obesity than does RYGBS, and typically result in loss of approximately 50% of excess body weight. Nonetheless, sales of such a device by one manufacturer (InaMed) are currently approximately $60M per year, indicating that there is a need for such therapy, despite requiring 65-78 minutes of invasive surgery to install the device, an efficacy limited to 38-45% excess weight loss in registration PMA studies, the need to periodically adjust the tightness of the band, and complications in approximately 10% of patients.
As such, there is a demonstrated need and market for improved weight loss devices.